Monoclonal antibodies and monoclonal antibody fragments with high specificities for human malignancies will be covalently coupled to DTPA via the cyclic DTPA anhydride technique to provide a means for labeling such agents with polyvalent metal radionuclides. The potential of radioimmunotherapy using monoclonal antibodies labeled with the alpha-emitting radionuclide fermium-255, (T1/2 = 20.1 h) and beta-emitting yttrium-90, T1/2 = 64.2 h) will be studied preclinically. Two gastrointestinal monoclonal antibodies with specificity for both colorectal and pancreatic carcinomas, 1083-17-1A (17-1A) and 1116-NS-19-9 (19-9), and a monoclonal antimelanoma antibody, 691-19-19 (19-19), will be investigated. Antibodies derivatized via the bifunctional chelate technique will be tested by a radioimmunoassay technique to verify their retention of immunological activity. Nude mice bearing the appropriate tumor type for each monoclonal antibody will be used to test the specificity of tumor uptake. Antibodies labeled with the gamma-emitting radionuclides indium-111, ytterbium-169, and yttrium-88 will be used for scintigraphic and tissue distribution studies to determine the time course of the tumor uptake of radiolabeled monoclonal antitumor antibodies. A radiolabeled monoclonal anti-influenza antibody will be used to control for nonspecific binding. The antibodies will then be labeled with Fm-255 and Y-90 as well as einsteinium-253 (a longer lived alpha emitter to be used as a model for Fm-255), and further tissue distribution studies will be carried out. These tissue distribution studies will be used for radiation dosimetry calculations. In vivo tumor growth studies in nude mice will be carried out to aid in assessment of the therapeutic potential of Fm255- and Y90-labeled monoclonal antibody derivatives. This multidisciplinary research approach, which combines the fields of bio-organic chemistry, immunochemistry, and radiopharmacology, is aimed at improving radioimmunotherapy methods for malignant processes in man.